In modern animal production systems, the equilibrium between the intestinal flora and host animal is a delicate one, and disturbance of this equilibrium (by e.g. bacterial infection) has a negative impact on the overall performance of the animals (Eckel, 1999). Knowledge about the problems of intestinal microbial infection in livestock opens the door to completely new ways of influencing the bio-regulatory processes through feed additives, reducing the frequency of diarrhea and even losses, by stabilising the intestinal flora. In the past, this infection problem was partially solved by supplying feeds containing antibiotics as growth promoter.
But today, 50 years since the discovery of the traditional antimicrobials (e.g. penicillin), a lot of bacteria are now resistant to one and, in many cases, to multiple antimicrobials (Guillot, 1989). This resistance is proving fatal for thousands of people each year and results in high medical and heavy economic costs (Barton, 1998). The problem of antimicrobial resistance is global, but is partially caused by the world-wide application of antimicrobials in animal nutrition, since addition of them to feed formulations resulted in better performance (decreased feed conversions and higher growth rates) (Dupont and Steele, 1987; Prescott, 1997) and since more than half of all antimicrobial use was associated with animal production (Aarestrup, 1999). For some countries, e.g. the European Union, this led already to a prohibition of all antimicrobials, usable as growth promoters in feed formulations (Muirhead, 1998; Ross, 1999).
The problem with most traditional antimicrobials and other growth promoters in use today is that they attack bacteria at the intracellular level (Guillot, 1989). That is, they inhibit key enzymes in the synthesis of compounds used to build up the cell. Whenever this approach is used, bacteria can develop mutations of the enzymes involved or can develop mechanisms to rapidly pump the antimicrobial out of the cell. Alternatively, they can develop enzymes, which directly degrade the antimicrobial (e.g. β-lactamase) (Neu et al., 1980; Chirica et al., 1998). By plasmid transfer (via microbial conjugation), resistance can be rapidly transferred from one microbial cell to another (expansion of resistance) (Finland, 1971; Hedges and Jacob, 1974; Thompson, 1986; Hamilton, 1994).
Since the world-wide negative response on the use of the traditional antimicrobials (as growth promoters) in animal feeds, research is performed to search for new types of (natural) antimicrobials or growth promoters (mainly with another mode of action) (Mazza, 1998). During research for alternative (natural) antimicrobials, attention is nowadays mainly focussed on the use of several (organic) acids (Eckel, 1997; Liang, 1997; Radecki et al., 1988), new active probiotics (Chiquette and Banchaar, 1998; Garriga et al., 1998; Tannock, 1999), prebiotics (Olsen, 1996; Bower et al., 1998; Brown et al., 1998; Iji and Tivey, 1998; Houdijk et al., 1999), some plant- (onions and garlic) and herb extracts (essential oils) (De Koning and Hongbiao, 1999; Nielsen, 1999).
Nowadays, different types of oligosaccharides are already used in different applications. In some of these applications, oligosaccharides are (covalently) linked to a support or carrier.
WO2006022542 claims the combined use of indigestible oligo-saccharides and digestible galactose saccharide for the manufacturing of a composition for use in a method for the treatment and/or prevention of respiratory tract infection and/or respiratory tract infection disease, said method comprising orally administering a composition to a mammal, said composition comprising a) a galactose containing indigestible oligo-saccharide containing at least two terminal saccharide units, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fucose; and b) at least 5 wt. % digestible galactose saccharide based on total dry weight of the composition, said saccharide being selected from the group consisting of galactose and digestible galactose containing saccharide containing at least two terminal saccharide units, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fucose. Dosage is 0.1 to 12 grams transgalactooligo-saccharides with a degree of polymerisation between 2 and 10 per 100 gram dry weight of the composition.
WO2004074496 relates to a process for the production of a novel oligo-saccharide, the process comprising combining a substrate with Lactobacillus α-galactosidase enzyme. The invention also relates to the oligo-saccharide itself and to compositions comprising it. The invention further relates to the use of the oligo-saccharide, as well as compositions comprising it, for increasing beneficial bacteria in the gastrointestinal tract of an animal. Said oligo-saccharide is composed of galactose and glucose.
JP2002226496 provides a method for obtaining an oligo-saccharide by hydrolyzing a polysaccharide without adding an acid and to obtain an anti-infectious disease agent containing the oligo-saccharide. Solution: A sulfated polysaccharide exemplified by fucoidan is hydrolysed by passing the sulfated polysaccharide through a H type cation exchange resin column containing a carboxy group and a sulfate group as exchange groups followed by heating to give the oligo-saccharide. The oligo-saccharide obtained by the method is mainly composed of fucose and exhibits activity as an anti-infectious disease agent against Escherichia coli, Vibrio, . . . , by a function of preventing pathogenic fungi from attaching to the intestinal tract.
CN1370784 describes the preparation process of chitinamine oligo-saccharide includes dissolution of chitinamine with acetic acid, enzyme adding reaction, addition of hydrochloric acid and final spray drying. It is characterized by the added enzyme comprising hemicellulase, cellulase and β-amylase and the pressure reduced evaporation during reaction. The process degrades chitinamine into chitinamine oligo-saccharidewith 2-12 chitinamines and average molecular weight of 1500. The chitinamine oligo-saccharide may be used in inhibiting tumor, preventing and treating hepatosis, improving intestinal tract function, preventing and treating senile diseases.
JP2002121138 states the production of a composition for the prophylaxis of intestinal tract infectious diseases capable of carrying out the prophylaxis of the infectious diseases caused by causative bacteria of the intestinal tract infectious diseases. Solution: This composition for the prophylaxis of the intestinal tract infectious diseases comprises one or more kinds selected from the group consisting of oligo-saccharides derived from hen's egg yolk, oligo-saccharide-bound proteins and oligo-saccharide-bound peptides. The composition is especially sialyloligo-saccharides, sialyloligo-saccharide proteins and sialyloligo-saccharide peptides. Furthermore, the composition has inhibitory actions on the adhesion of the causative bacteria of the intestinal tract infectious diseases to host cells.
U.S. Pat. No. 6,069,137 describes a method for the treatment of traveller's diarrhoea mediated by enterotoxigenic E. coli in a subject, which method comprises administering to a subject in need of such treatment an effective amount of a composition comprising an oligo-saccharide sequence selected from the group consisting of β-Gal(1-4).β-Glc, .β.Gal(1-3).β.GalNAc, β.GalNAc(1-4).β.Gal, β.Gal(1-3).β.Gal, β.Gal(1-3).β.GalNAc(1-4).β.Gal and α.NeuAc(2-3).β.Gal covalently attached to derivatized silica particles, wherein said oligo-saccharide sequence binds at least one serotype of enterotoxigenic E. coli, and wherein said composition is capable of being eliminated from the gastrointestinal tract.
EP1018342 describes the use of an agent in the preparation of a medicament for the prevention or treatment of an enteric infection mediated by an SLT, wherein said agent is a pharmaceutically acceptable solid inert affinity support capable of being eliminated from the gastrointestinal tract, which support has an affinity ligand covalently attached thereto through a spacer arm, wherein said ligand is characterized as an oligo-saccharide containing the disaccharide subunit αGal(1-4).βGal which binds the SLT; with the proviso that the disaccharide is not part of a αGal(1-4)ssGal(1-4).βGlcNAc trisaccharide or a αGal(1-4)ssGal(1-4).βGlc trisaccharide.
U.S. Pat. No. 5,939,397 describes a method to treat cholera and electrolyte imbalance and diarrhoea caused by V. cholera infection in a subject, which method comprises administering to a subject in need of such treatment an effective amount of a composition comprising an oligo-saccharide sequence covalently attached to a pharmaceutically acceptable solid, inert support through a non-peptidyl compatible linker arm, wherein said oligo-saccharide sequence when so bound to said solid, inert support is capable of binding one or more serotypes of V. cholerae, and wherein said composition is capable of being eliminated from the gastrointestinal tract. Said oligo-saccharide is a 1-3 oligo-saccharide.
An object of the present invention is to provide a more specific and more active range of oligosaccharides having improved effects on the microbial ecosystem in the gastrointestinal tract. More in particular, the invention aims to provide a specific range of oligosaccharides for selectively controlling and regulating the microbial ecosystem in the gastrointestinal tract of a subject in need thereof, by specific enumeration of enteric pathogens followed by specific excretion thereof. When applied as a (feed) composition to animals, it is believed that said activity surprisingly results in an effective (feed) composition resulting in a improved feed conversion ratio (being the weight feed consumed per kg body weight gain) and improved feed value, health and well-being of the animal.